•PFAS exposure associated with systolic and diastolic blood pressure in pregnancy.•No clear associations between PFAS exposure and PE or GH were found.•Blood pressure increase was small but at a ...population level this may increase hypertension.•This has potential long term health implications for both the mother and the child.
Previous studies of association between exposure to poly- and perfluoroalkyl substances (PFAS) and gestational hypertension (GH) and preeclampsia (PE) have shown conflicting results, but most dichotomized outcome and did not study continuous blood pressure (BP) changes.
To study the association between PFAS exposure in early pregnancy and maternal BP trajectories in pregnancy, gestational hypertension and preeclampsia.
1436 women were enrolled in the Odense Child Cohort in early pregnancy and had a serum sample drawn, from which perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) were measured using LC–MS/MS. Repeated BP measurements through pregnancy and information on PE were obtained from hospital files. Adjusted linear mixed models were used to investigate association between PFAS exposure and BP trajectory. Associations between PFAS and PE and GH were assessed by Cox proportional hazards model.
All women had measurable concentrations of PFAS. In all of many comparisons higher PFAS exposure (apart from PFHxS) was associated with higher systolic (SBP) and diastolic (DBP) blood pressures, although not all were significant, which is unlikely to be due to chance. After adjustment, each doubling in PFOS or PFOA exposure was associated with 0.47 mmHg (95% CI: −0.13; 1.08) and 0.36 mmHg (−0.19; 0.92) higher SBP; and 0.58 mmHg (0.13; 1.04) and 0.37 mmHg (−0.05; 0.79) higher DBP. No clear associations between PFAS exposure and PE or GH were found.
The magnitude of the association between PFAS exposure and BP might appear small, statistically non-significant and the possible clinical importance low. However, at a population level this may slightly shift the distribution of BP towards an increased incidence of GH. If BP increases in pregnancy, it may have long-term impact on health not only of the pregnant woman but also of her offspring.
Perfluorinated alkylated substances (PFAS) have been extensively used in consumer products and humans are widely exposed to these persistent compounds. A recent study found no association between ...exposure to perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) and miscarriage, but no studies have examined adverse effect of the more recently introduced PFASs. We therefore conducted a case-control study within a population-based, prospective cohort during 2010-2012. Newly pregnant women residing in the Municipality of Odense, Denmark were invited to enroll in the Odense Child Cohort at their first antenatal visit before pregnancy week 12. Among a total of 2,874 participating women, 88 suffered a miscarriage and 59 had stored serum samples, of which 56 occurred before gestational week 12. They were compared to a random sample (N=336) of delivering women, who had also donated serum samples before week 12. Using a case-control design, 51 of the women suffering a miscarriage were matched on parity and gestational day of serum sampling with 204 delivering women. In a multiple logistic regression with adjustment for age, BMI, parity and gestational age at serum sampling, women with the highest tertile of exposure to perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) in pregnancy had odds ratios for miscarriage of 16.5 (95% CI 7.4-36.6-36.5) and 2.67 (1.31-5.44), respectively, as compared to the lowest tertile. In the matched data set, the OR were 37.9 (9.9-145.2) and 3.71 (1.60-8.60), respectively. The association with perfluorohexane sulfonic acid (PFHxS) was in the same direction, but not statistically significant, while no association was found with PFOA and PFOS. Our findings require confirmation due to the possible public health importance, given that all pregnant women are exposed to these widely used compounds.
Pregnancy-induced hypertension is a severe pregnancy complication, increasing risk of long-term cardiovascular disease in mothers and offspring. We hypothesized that maternal blood pressure in ...pregnancy associated with offspring blood pressure; that the associations were sex-specific; and that maternal circulating placental angiogenic markers (PlGF placental growth factor and sFlt-1 soluble fms-like tyrosine kinase-1) mediated this relationship. We analyzed data from 2434 women and 2217 children from the Odense Child Cohort, a prospective Danish cohort study. Offspring blood pressure trajectory from 4 months to 5 years was highly associated to maternal first, second, and third trimester blood pressure, and mean blood pressure in pregnancy, independent of maternal and offspring covariates. There were offspring sex-specific associationsGirls from mothers in the highest quartile of first and third trimester blood pressure had significantly higher systolic blood pressure at 5 years than the rest of the cohort (mean difference±SEM1.81±0.59 and 2.11±0.59 mm Hg, respectively, all P<0.01); whereas boys had significantly higher diastolic blood pressure at 5 years (mean difference±SEM1.11±0.45 and 1.03±0.45, respectively, all P<0.05). Concentrations of PlGF at gestational week 28 correlated inversely to maternal gestational blood pressure trajectory, independent of the diagnosis of pregnancy-induced hypertension, adjusted β coefficients (95% CI) for predicting systolic blood pressure (SBP)−3.18 (−4.66 to −1.70) mm Hg, for predicting diastolic blood pressure (DBP)−2.48 (−3.57 to −1.40) mm Hg. In conclusion, maternal gestational blood pressure predicted offspring blood pressure trajectory until 5 years in a sex-differential manner. Furthermore, subtle alterations in blood pressure in early pregnancy preceded hypertension or preeclampsia, and PlGF was a mediator of cardiovascular health in pregnancy.
The mineralocorticoid aldosterone increases in plasma in healthy pregnancy along with renin and angiotensin II and plays a key role in the physiological plasma volume expansion. In mice, aldosterone ...contributes to an optimal fetal development by enhancing PlGF (placental growth factor) expression and trophoblast cell proliferation. In preeclampsia, there is coincident suppression of aldosterone and impaired placental development. We hypothesized that aldosterone independently contributes to placental and birth weight in humans, and high dietary sodium and low potassium intakes affect this relationship adversely. We analyzed 24-hour urine collections and plasma samples from gestational week 29 in a subsample of 569 pregnant women from the Odense Child Cohort—a Danish population-based longitudinal cohort study. Plasma and urinary aldosterone were measured by ELISA, sodium and potassium excretions by flame photometer. Predictive values of aldosterone levels and sodium and potassium intakes were assessed by multiple and Cox regression analyses. Primary outcomes were placental weight and birth weight. Secondary outcome was preeclampsia. Urinary aldosterone excretion at gestational week 29 independently contributed to placental and birth weights (adjusted β-coefficients 95% CI, 24.50 9.66–39.35 and 9.59 4.57–14.61, respectively). Aldosterone levels were not associated to preeclampsia incidence. Salt intake >6 g/d was associated with development of preeclampsia (hazard ratio 95% CI, 5.68 1.51–21.36). At gestational week 29, urinary aldosterone excretion is an independent predictor of placental and birth weights. High salt intake is a risk factor for preeclampsia. In perspective, suppression of aldosterone in pregnancy has adverse trophic effects.
Albuminuria in the pathological range is a significant predictor of preeclampsia. In healthy persons, high normal urinary albumin predicts a later incidence of hypertension and is associated with ...salt sensitivity of blood pressure. We hypothesized that in pregnancy urinary albumin in the normal range associates with blood pressure through activation of distal Na
+
reabsorption and renal salt retention by plasma factors cofiltered with albumin. We analyzed 24-h urine collections and plasma samples from gestational week 29 of 560 pregnant women from the Odense Child Cohort, a Danish population-based cohort. Plasma and urinary aldosterone were measured by ELISA. Plasma and urinary Na
+
, K
+
, Cl
−
, and creatinine were also determined. Predictive values of urinary albumin were assessed by linear mixed, multiple, and Cox regression analyses. Primary outcomes were blood pressure and renal electrolyte handling. Twenty-four-hour urinary albumin excretion at gestational week 29 associated with gestational blood pressure trajectory, with adjusted β coefficients (95% confidence intervals) for each 10-fold increase in urinary albumin as follows: 5.71 (1.60 to 9.81) mmHg for systolic blood pressure and 4.39 (1.41 to 7.38) mmHg for diastolic blood pressure. Urinary albumin was inversely associated with fractional excretion rates of Na
+
, K
+
, and Cl
−
, with adjusted β coefficients (95% confidence intervals) for each 10-fold increase in urine albumin as follows: −0.25 (−0.35 to −0.14), −5.06 (−6.81 to −3.30), and −0.28 (−0.41 to −0.15), respectively. In conclusion, at gestational week 29, urinary albumin excretion in the normal range associated with blood pressure and renal electrolyte handling independent of potential confounders.
The angiogenic factor ratio soluble Fms-kinase 1 (sFlt-1)/placental growth factor (PlGF) is a novel diagnostic tool for preeclampsia. We compared the efficacy of the KRYPTOR (BRAHMS) automated assays ...for sFlt-1 and PlGF with the Elecsys (Roche) assays in a routine clinical setting. Preeclamptic women (n = 39) were included shortly after the time of diagnosis. Normotensive control pregnancies were matched by gestational age (n = 76). The KRYPTOR assays performed comparably or superior to Elecsys (sFlt-1/PlGF area under the curve 0.746 versus 0.735; P = .09; for non-obese 0.820 versus 0.805, P = .047). For early-onset preeclampsia, KRYPTOR area under the curve increased to 0.929 with a 100% specificity for preeclampsia at cut-off 85 and an 88.9% sensitivity for preeclampsia at cut-off 33. For women with preeclampsia and preterm delivery or Hemolysis, Elevated Liver enzymes, Low Platelet count (HELLP) syndrome, the KRYPTOR sFlt-1/PlGF ratio was manifold increased (P < .01). The sFlt-1/PlGF ratio proved especially useful in early-onset preeclampsia, preeclampsia with preterm delivery or HELLP, and among non-obese women.
Background Low foetal vitamin D status may be associated with higher blood pressure (BP) in later life. Objective To examine whether serum 25-hydroxyvitamin D2+3 (s-25OHD) in cord and pregnancy ...associates with systolic and diastolic BP (SBP; DBP) in children up to 3 years of age. Design Prospective, population-based cohort study. Methods We included 1594 singletons from the Odense Child Cohort with available cord s-25OHD and BP data at median age 3.7 months (48% girls), 18.9 months (44% girls) or 3 years (48% girls). Maternal s-25OHD was also assessed at gestational ages 12 and 29 weeks. Multiple regression models were stratified by sex a priori and adjusted for maternal educational level, season of birth and child height, weight and age. Results In 3-year-old girls, SBP decreased with −0.7 mmHg (95% CI −1.1; −0.3, P = 0.001) and DBP with −0.4 mmHg (95% CI −0.7; −0.1, P = 0.016) for every 10 nmol/L increase in cord s-25OHD in adjusted analyses. Moreover, the adjusted odds of having SBP >90th percentile were reduced by 30% for every 10 nmol/L increase in cord s-25OHD (P = 0.004) and by 64% for cord s-25OHD above the median 45.1 nmol/L (P = 0.02). Similar findings were observed between pregnancy s-25OHD and 3-year SBP, cord s-25OHD and SBP at 18.9 months, and cord s-25OHD and DBP at 3 years. No consistent associations were observed between s-25OHD and BP in boys. Conclusion Cord s-25OHD was inversely associated with SBP and DBP in young girls, but not in boys. Higher vitamin D status in foetal life may modulate BP in young girls. The sex difference remains unexplained.
We tested the controversial hypothesis that vitamin D depletion aggravates hypertension and target-organ damage by influencing renin.
Four-week-old double-transgenic rats (dTGR) with excess ...angiotensin (Ang) II production due to overexpression of the human renin (hREN) and angiotensinogen (hAGT) genes received vitamin D-depleted (n=18) or standard chow (n=15) for 3 weeks. The depleted group had very low serum 25-hydroxyvitamin D levels (mean±SEM; 3.8±0.29 versus 40.6±1.19 nmol/L) and had higher mean systolic BP at week 5 (158±3.5 versus 134.6±3.7 mm Hg, P<0.001), week 6 (176.6±3.3 versus 162.3±3.8 mm Hg, P<0.01), and week 7 (171.6±5.1 versus 155.9±4.3 mm Hg, P<0.05). Vitamin D depletion led to increased relative heart weights and increased serum creatinine concentrations. Furthermore, the mRNAs of natriuretic peptides, neutrophil gelatinase-associated lipocalin, hREN, and rRen were increased by vitamin D depletion. Regulatory T cells in the spleen and in the circulation were not affected. Ang metabolites, including Ang II and the counter-regulatory breakdown product Ang 1 to 7, were significantly up-regulated in the vitamin D-depleted groups, while ACE-1 and ACE-2 activities were not affected.
Short-term severe vitamin D depletion aggravated hypertension and target-organ damage in dTGR. Our data suggest that even short-term severe vitamin D deficiency may directly promote hypertension and impacts on renin-angiotensin system components that could contribute to target-organ damage. The findings add to the evidence that vitamin D deficiency could also affect human hypertension.
Purpose: To investigate the predictive performance of placental growth factor (PlGF) and soluble FMS-like kinase 1 (sFlt-1) on birth weight and small for gestational age (SGA), in a large, ...population-based cohort.
Methods: Women enrolled in the population-based, prospective Odense Child Cohort Study with early (GA < 20 weeks) and/or late (≥20 weeks) pregnancy blood samples (n = 1937) were included. The association between log-transformed values of the biomarkers and birth weight Z-score was studied using multivariate regression models. The prediction of SGA overall, and in women developing preeclampsia, by biomarkers was evaluated using receiver operating characteristic analyses.
Results: No substantial associations between early pregnancy biomarkers and SGA were seen. PlGF measured in late pregnancy demonstrated the strongest association with birth weight Z-score (adjusted β-coefficient = 0.43 95%CI = 0.35; 0.50). The area under curve (AUC) for predicting SGA was higher for sFlt-1/PlGF compared to sFlt-1 (0.74 versus 0.63, p = .006) and reached excellent prediction for SGA after preeclampsia (AUC 0.94). Optimal sFlt-1/PlGF ratio cut-offs had higher negative predictive value (NPV) and positive predictive value (PPV) for SGA (cut-off > 5.0; NPV = 99.1%, PPV = 5.4%) compared to each marker individually.
Conclusion: The sFlt-1/PlGF ratio is a potential predictor of SGA in population-based screening, particularly when preeclampsia is also present.
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